Herpes simplex viruses types 1 and 2 (HSV1 and HSV2) infect skin and mucous membranes to cause acute lesions, which resolve within a matter of days. However, during the course of this infection virus is transported to the neurons that innervate the locally infected site and establish a lifelong latent persistence. Generally, the acute infections of the mouth, eye, and other facial regions are caused by HSV1, with the establishment of latency in the trigeminal ganglia, whereas acute infections of the genital areas are due to HSV2, with the establishment of latency in the lumbar and sacral ganglia. In both cases, lifelong latency is punctuated periodically by production of infectious virions in the ganglia, transport to the innervated epithelial tissue, and bouts of acute virus replication, shedding of infectious virus from the acutely infected site, and perhaps local lesion formation. These lesions are the familiar cold sores, which occur around the lips, herpes keratitis of the eye, and the venereal disease of the anal/genital region.
In addition to these common clinical experiences, herpes simplex viruses may also cause life-threatening encephalitis both in neonates, usually the result of massive virus exposure during birth, and in immuno-compromised adults. Herpetic encephalitis results in high mortality, and survivors are often severely handicapped. Herpetic encephalitis occurs in about 3000 newborns each year in the USA. Often this results because of massive exposure of the neonate to virus (usually HSV2) shed in the birth canal of the infected mother, and is of greatest probability if the membranes have ruptured and if the mother is experiencing a primary genital herpetic infection. The infected newborn may experience localized skin and ocular lesions, viremia, and localized central nervous system lesion development, usually starting within 6 days of birth. If infection results in disseminated disease, central nervous system (CNS) disease occurs in up to 50% of the infants and can result in 75% mortality. For the survivors of CNS involvement the outcome is bleak, with psychomotor retardation in 50 to 75% of the survivors.
The compound 2-phenylamino-6-oxo-9-(4-hydroxybutyl)purine, HBPG (U.S. Pat. No. 5,646,155) has been shown to reduce the frequency of hyperthermia-induced HSV1 and HSV2 reactivation in mice and reduce the amount of viral DNA in the relevant nerve ganglia. In addition, HBPG has been shown to reduce the frequency of recurrent ocular HSV1 disease in squirrel monkeys.